Heparin-binding EGF-like growth factor (HB-EGF) is a mitogen for fibroblasts, keratinocytes, and vascular smooth muscle cells that is produced by macrophages. Experiments characterizing the factors found in pig dermal wound fluid have indicated that HB-EGF is responsible for a significant proportion of the mitogenic activity in the fluid, and that it can act synergistically in vitro with another factor in the fluid, platelet-derived growth factor (PDGF). Given these results, a project has been initiated with the long-term objective of determining whether HB-EGF can be used as a human therapeutic agent to accelerate healing, either alone or in combination with other growth factors such as PDGF. During Phase I of the project, bacterial recombinant HB-EGF was produced and shown to indeed accelerate wound closure of full-thickness wounds in diabetic (db/db) mice. During Phase II, these wound healing experiments will be expanded to examine the effects of varying the dose of HB-EGF, and of mixing HB-EGF with PDGF. Recombinant expression of HB-EGF in mammalian cells will also be explored, to determine whether a more active form of HB-EGF can be produced. Finally, the large-scale production of either bacterial or mammalian recombinant HB-EGF will be initiated.